The following description of the background of the invention is provided simply as an aid in understanding the invention and is not admitted to describe or constitute prior art to the invention.
Glaucoma is the second most common cause of blindness in the United States. It is estimated that some two million Americans have glaucoma, with half of those suffering unaware of the presence of the disease. Primary open-angle glaucoma (“POAG”) is the most common form of glaucoma, accounting for some 60 to 70% of all glaucomas.
POAG is characterized by obstruction of the normal aqueous outflow of fluids through the trabecular meshwork, canal of Schlemm, intrascleral channels, and episcleral and conjunctival veins. In open-angle glaucoma, this obstruction exists despite an angle that appears open. Generally, a patient that has not been otherwise diagnosed as having glaucoma first becomes aware of the disease due to losses in the visual field. By this point, the degree of optic nerve atrophy resulting from the disease may be quite severe, and is irreversible. Thus, early diagnosis and treatment play a key role in patient management.
Several risk factors have been identified as being related to POAG, including elevated intraocular pressure (“IOP,” 50% of patients present with an IOP of <22 mm Hg), increased age (POAG is 6× more common in persons >60 years of age), a family history of the disease (a 15× increased chance of developing glaucoma), race (African Americans are at an increased risk for more serious disease), diabetes, hypertension, myopia, and the use of corticosteroids.
While elevated IOP is a primary risk factor for development of POAG, about ⅙ of patients exhibit an IOP within the normal range. Additionally, there is currently no reliable method for predicting which patients presenting with elevated IOP will progress to POAG. Recently, the relationship of the trabecular meshwork-inducible glucocorticoid response (“TIGR”) gene and protein have been studied for possible associations with glaucoma and related diseases. See, e.g., U.S. Pat. Nos. 5,861,497, 5,916,778, 5,925,748, and 6,248,867; Morissette et al., Nat. Genet. 19: 319-21 (1998); Brezin et al., Am. J. Med. Genet. 76: 438-45 (1998); Shimizu et al., Am. J. Ophthalmol. 130: 165-77 (2000); Nguyen et al., J. Biol. Chem. 273: 6341-50 (1998); and Lindblad-Toh et al., Nat. Genet. 24: 381-6 (2000). Each publication and patent in the foregoing section is hereby incorporated by reference in its entirety, including all tables, figures, and claims.